Oxidative Stress and Antiaging Medicine: Oxidative Stress Response and Antiaging

Aerobic organisms, including humans, can efficiently produce adenosine triphosphate (ATP) using oxygen in the air. However, 1–2% of the oxygen consumed becomes a reactive oxygen species (ROS) called superoxide (O2˙), and mitochondria are constantly exposed to oxidative stress [1]. In addition, a large amount of ROS is produced from inflammatory cells such as neutrophils, and the body is exposed to strong oxidative stress. At the same time, the body is exposed to various stimuli, not only from within the body but also from what is called the exposome (ultraviolet rays, radiation, tobacco, alcohol, food additives, environmental hormones, etc.), and is exposed to oxidative stress from outside the body. Therefore, from the standpoint of antiaging, it is required to maintain a body and cells that can overcome ROS from both inside and outside the body. Now, when cells are exposed to oxidative stress, for example, when exposed to ultraviolet rays, many people seem to think that the stimulation by ROS [hydroxyl radicals (OH˙) and singlet oxygen (1O2˙)] directly produced by ultraviolet rays leads to cell damage. However, when human keratinocytes are irradiated with ultraviolet rays of intensity that can cause cell death, the ROS directly produced by the ultraviolet rays are actually at the level of several μM when converted to hydrogen peroxide, and the irradiation time is also a few minutes. Considering that it is a ROS with a very short half-life, there is almost no possibility that HaCaT keratinocytes (human keratinocytes) will be damaged by the ROS directly produced by ultraviolet rays. Also, as is widely known, it has been found that applying sunscreen after sunburn suppresses skin inflammation. From the above, it can be considered that the response of cells when exposed to exogenous oxidative stress is not due to ROS from the outside, but to ROS produced secondarily inside the cells after stimulation from the outside. In other words, endogenous ROS become second messengers, and downstream transcription factors and gene expression are induced, leading to complex cellular responses. The mechanisms of cell death due to exogenous oxidative stress, transcription factors, gene expression control, etc., will be left to other sections, and in this section, we will focus on ROS produced secondarily inside cells due to exogenous stimuli.